Pregnancy evolved multiple times independently in a diversity of species and habitats and displays one of the best examples of convergent evolution. Its evolution entails drastic morphological, physiological and immunological adaptations. Yet research focused predominantly on mammalian pregnancy where both Major Histocompatibility Complex pathways (MHC I and II) are suppressed to prevent semi-allogenic embryo rejection. Studying the unique male pregnancy evolution in pipefishes and seahorses (Syngnathiformes), we hypothesized that along their evolution from oviparity to male pregnancy the adaptive immune system re-arranged. Our comparative genomic analyses uncovered impairment and loss(es) of key MHC II pathway genes. From a shared functional loss of invariant chain (CD74), remodelling of seahorse and pipefish adaptive immune systems has taken distinct evolutionary routes: while the genus Syngnathus has lost its entire MHC II pathway and reorganized its MHC I gene repertoire, the genus Hippocampus’ MHC II pathway genes instead diverged markedly. For unravelling this unique male pregnancy evolution, we further assessed the repertoire of genes that is differentially expressed in male pregnancy of pipefishes and seahorses and found an overlap with well-known mammalian immune and pregnancy genes. The unexpected flexibility in vertebrate immune systems may yield novel insights into immunodeficiency imposed by viral disease in other vertebrates that attack precisely this pathway. We are currently conducting tissue transplant and immunological stimulation experiments and are using genetic manipulation via CRISPR/cas9 in other teleost systems to shed light on the function of these as yet unique immunological adaptations.