Abstract Nowadays, the cultivation mode of Hyriopsis cumingii urgently needs transformation and upgrading, and realizing sustainable aquaculture lacks the selection of suitable algae and the exploration of culture conditions. This experiment is to evaluate combined effects of ration levels (low ration, medium ration and high ration) and temperature (13.0 ± 0.2°C, 23.0 ± 0.2°C, and 33.0 ± 0.2°C) on immune responses of H. cumingii. Activities of immune enzymes (alkaline phosphatase, superoxide dismutase, catalase and lysozyme) and expression of immune‐related genes (interleukin‐17 and inhibitor of apoptosis protein) in mussels were analysed during 21 days exposure period. Results suggested that the diatom Navicula pelliculosa was suitable algae for H. cumingii, the optimal ration level and temperature of H. cumingii were the medium ration and 23℃. Semi‐starvation, excessive dietary, low‐ or high‐temperature stimulated immune activities, and when beyond the immune regulation range, most immune enzyme activities decreased. Acute stress also stimulated expression of HcIL‐17 and IAP, and long‐term stress of discomfort temperature and ration levels led to immune dysfunction and affected expression of these genes. The study has practical significance in realizing the sustainable aquaculture of H. cumingii and provides a broader perspective regarding the water ecosystem.
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