Abstract Modern livestock breeding includes immunogenetic aspects in order to address disease resistance, health and welfare. In domestic pigs positive and negative associations between immune and performance traits have been observed. Little is known about the underlying genetic factors, however, since the pig is increasingly recognized as a suitable biomedical model new insights on the porcine immune system and physiology can be beneficial for medical science. Here, studies on porcine immune responsiveness are based on tetanus toxoid (TT) vaccine as experimental antigen to induce a comprehensive cellular and humoral immune response. The response to TT was studied by transcriptomic microarray analysis of peripheral blood mononuclear cells (PBMC). Differences of relative mRNA abundances between time stages and phenotypes identified numerous affected signaling pathways. Analyses of divergent phenotypes differentiated for high and low lean growth performance and high and low antibody (AB) titers, clearly identified high lean growth to be associated with increased transcript numbers in pathways of the adaptive immune system. Differentiation between initial and secondary responses revealed that phenotype-related differences appear in the adaptive immune response: high lean growth animals activate numerous immune response pathways including B cell signaling as most significant in the subgroup of high AB but T cell signaling as predominant in low AB animals. Explanations can be drawn from literature reports that have shown that pig selection for lean body composition influences the growth hormone-insulin-like growth factor 1-axis which in case of high activation can be expected to provide an advantageous immune status. Moreover, low lean growth, i.e. fat accumulation, can be seen as precursor of obesity and recent research on obese human and mice has shown chronic inflammation and insulin resistance in adipose tissue which eventually cause an impaired systemic immunocompetence.