The genes were selected based on the following strategies: (1) genes with significant DE levels between the phenotypes of interest that spanned a dynamic range of at least log2 (ratio) > 0.485; (2) genes with a coefficient of determination greater than 0.8 with respect to the first principal component in the PCA; and (3) genes with biological interest (e.g.SLA-1andIL10RA;Additional file3). molecular phenotype to refine ITs in pig and to identify potential biomarkers that can provide new insights into immune response analysis. Keywords:Biomarkers, Blood, Pig, Transcriptome, Immune response == Background == Over the last decades, production traits have been studied and exploited for the genetic improvement of livestock through selective breeding [1]. At the same time, diseases that can cause substantial economic losses have emerged. There is little doubt about the economic and welfare implications of infectious diseases or about the presence of genetic variation in disease susceptibility and resistance in livestock populations [2]. However, research aimed at identifying genetic factors that confer relative susceptibility or resistance against diseases in pigs is limited by the lack of sufficient phenotypic observations. Thus, alpha-Amanitin including health traits in the current breeding schemes while limiting loss in long-term selected production traits is a major concern and stands as an emerging trend in pig breeding [1,3-6]. Direct strategies that target animal resistance or tolerance to specific pathogens, may result in increased susceptibility to other diseases [7]. Therefore, we and other authors have suggested an indirect approach focused on immunity traits (ITs) [3,7,8]. ITs measured on healthy animals are studied as candidate traits for immune capacity. To define immune capacity or immunocompetence, it is necessary to know how the immune system of an individual responds to different stimuli (e.g. contamination by microorganisms, vaccination or environmental stresses), and its efficiency. Therefore, the term immunocompetence may be defined as the ability of the host to launch an immune response SMN of sufficient specificity and magnitude, and thus is a rough indication of the effective quality of the hosts immune system [9,10]. For instance, in poultry for which many studies are available, Heet al.[11] demonstrated that chicken lines with functionally less active heterophils (equivalent to mammalian neutrophils) were more susceptible to infections bySalmonella enteritidisthan those with highly functional heterophils. Furthermore, Swaggertyet al. [12] reported that broilers selected for higher levels of pro-inflammatory cytokines and chemokines had a more efficient pro-inflammatory profile that contributed in part to increased resistance against pathogens. Thus, identifying candidate ITs that could predict immunocompetence is a major issue in animal production systems. We and others have shown that a large number of ITs are heritable, which suggests that genetic selection on ITs is usually feasible [7,13]. The new challenge is to identify heritable ITs that are significantly associated with health or disease resistance and may predict the efficiency of an individuals immune response before biotic or abiotic stresses occur [14]. Peripheral blood cells are now widely used as a surrogate tissue to monitor individuals for various markers [15]. Blood cells constitute one of the first lines of the immune defence system [16]. For studies on immunocompetence, blood is considered as a target tissue that contains the different immune cells that circulate in the whole body. Indeed, profiling gene transcripts in blood has earned its place in the molecular and cellular profiling approaches used to analyse the immune response in patients with a wide range of diseases in humans [17]. Moreover, analysis of the blood transcriptome can contribute to identify immune response specific signatures (overexpressed or under-expressed transcripts) associated with specific ITs, which might be translated into useful molecular biomarkers for differential immunocompetence. Ultimately these biomarkers or patterns of markers could help to improve animal selection programs. Huanget al.[18,19] and Arceoet al.[19] have shown that pig blood transcriptome is informative to monitor disease susceptibility, to characterize response to immune alpha-Amanitin stimulation [20] or to refine the characterization of certain ITs [8]. In the present study, our first objective was to perform blood transcriptome profiling in alpha-Amanitin pigs with extreme IT levels and without any initial focus on resistance to specific pathogens. Our second objective was to investigate whether genome-wide transcriptional data in blood can lead to the identification of candidate biomarkers associated with variations of ITs. == Results == == The blood transcriptome varies significantly for four of the eight ITs tested == Eight ITs were considered in an extreme phenotype study design (Table1). The ITs were classified into two subsets corresponding to (1) ITs measured afterin vitrostimulation (IL2, IL10, IFN, TNF and.