Pygmy sperm whale multi-omics data reveal hypoxia adaptations in deep-diving cetaceans

Deep-diving cetaceans tolerate acute hypoxia better than their terrestrial ancestors and shallow-diving counterparts. However, our poor understanding of how genetic factors, cellular functions, and physiological characteristics combine to drive hypoxia adaptation in deep-diving cetaceans remains a critical gap.

Here, we studied the genetic basis for this ability by creating a de novo genome assembly for the pygmy sperm whale (Kogia breviceps) and comparatively analyzing genomes from 12 cetacean species, including 2 other deep-diving cetaceans. We also sequenced and compared single-nucleus RNA data from the muscle and heart of the pygmy sperm whale and its terrestrial relative Bos taurus. We found that genetic and cellular changes in the HIF-1 pathway, electron transport chain, glucose and fatty acid catabolism, and heart rate may contribute to hypoxia tolerance in deep-diving cetaceans. Key adaptations include rapid evolution of glycolysis-related genes (PYGM and ENO3), differential expression of HIF-1 pathway genes like ARNT, and accelerated conserved noncoding elements in genes such as ATP5F1E (ATP synthase) and DMD (dystrophin). We found an increase in myocytes and type II cardiomyocytes in the pygmy sperm whale's muscle and heart tissues, which may support energy metabolism and homeostasis during deep dives.

These findings suggest deep-diving cetaceans have unique genetic and cellular adaptations to cope with hypoxia, offering insights into how mammals handle low oxygen levels at the cellular level.