Comparative Cochlear Transcriptomics in Echolocating Bats and Mouse Reveals Hras as Protector Against Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL), caused by irreversible cochlear hair cell (HC) damage, lacks effective therapies due to a limited understanding of endogenous protective mechanisms. The echolocating bats exhibit natural resistance to intense noise, and this suggested novel insights into methods to protect against NIHL. Here, through comparative transcriptomic analysis of noise-exposed cochleae from the eastern bent-winged bats (Miniopterus fuliginosus) and mice, the specific transcriptional dynamics in noise-resistant Miniopterus fuliginosus are revealed, thus highlighting potential mechanisms for preventing cochlear damage that mouse models cannot replicate, with Hras emerging as the most significant hub upregulator. Functional validation in mice demonstrates that HC-specific Hras overexpression significantly attenuates noise-induced HC death, synaptic loss, and auditory threshold shifts. Mechanistically, Hras confers protection by activating the PI3K/Akt signaling pathway, a critical pro-survival cascade. The findings further disentangle the mechanisms of cochlear resistance to intense noise in echolocating bats and suggest that targeting Hras expression may be a potential therapeutic intervention against NIHL.