Sperm infertility or subfertility is detrimental to the precious highland germplasm like yak whose population has been gradually declining in India. Understanding the ‘omic’ landscape of infertile or subfertile yak sperm can reveal some interesting insights. In an attempt to do the same, this study considered the semen of infertile or subfertile yak bulls for whole-genome and transcriptome evaluations. DNA sequencing revealed that the yak sperm genome contains the necessary genes to carry out all the important biological processes related to the growth, development, survival and multiplication of an organism. Interestingly, RNA Seq results highlighted that genes like VAMP7, MYLK, ARAP2 and MARCH6 showed increased expression, while biological processes related to immune response (GO:0043308, GO:0002447, GO:0002278, GO:0043307, GO:0043312, GO:0002283, GO:0043299 and GO:0002446) were significantly overrepresented. These findings hint at a possible role played by immune system in regulating infertility or subfertility in yaks. Further, in-depth studies can validate these findings and help in improving our biological understanding in this area.