Abstract

Simple Summary Epinephelus akaara is a highly valuable aquaculture species in the Asia-Pacific region. However, intensive farming and live transport often expose it to low oxygen conditions, resulting in substantial economic losses. This study investigated the hypoxic response of Epinephelus akaara by analyzing hepatic gene expression and enzymatic activities following 9 h of hypoxia exposure. The results demonstrated that acute hypoxia at 6–9 h induced significant alterations in genes associated with energy metabolism, immune response, and apoptosis, with activation of key signaling pathways including HIF-1, IL-17, and PI3K/Akt. Enzyme activities related to energy production and immune function also exhibited significant changes during this critical period. These findings reveal that 6–9 h is a critical window period for physiological stress and adaptation to hypoxia in E. akaara. These results can support the development of hypoxia tolerant varieties to improve the sustainability of grouper farming and reduce losses.