Background Immune traits (ITs) are potentially relevant criteria to characterize an individual's immune response. Our aim was to investigate whether the peripheral blood transcriptome can provide a significant and comprehensive view of IT variations in pig. Results Sixty-day-old Large White pigs classified as extreme for in vitro production of IL2, IL10, IFNγ and TNFα, phagocytosis activity, in vivo CD4⁻/CD8⁺ or TCRγδ + cell counts, and anti-Mycoplasma antibody levels were chosen to perform a blood transcriptome analysis with a porcine generic array enriched with immunity-related genes. Differentially expressed (DE) genes for in vitro production of IL2 and IL10, phagocytosis activity and CD4⁻/CD8⁺ cell counts were identified. Gene set enrichment analysis revealed a significant over-representation of immune response functions. To validate the microarray-based results, a subset of DE genes was confirmed by RT-qPCR. An independent set of 74 animals was used to validate the covariation between gene expression levels and ITs. Five potential gene biomarkers were found for prediction of IL2 (RALGDS), phagocytosis (ALOX12) or CD4⁻/CD8⁺ cell count (GNLY, KLRG1 and CX3CR1). On average, these biomarkers performed with a sensitivity of 79% and a specificity of 86%. Conclusions Our results confirmed that gene expression profiling in blood represents a relevant molecular phenotype to refine ITs in pig and to identify potential biomarkers that can provide new insights into immune response analysis.