Integrative Analysis of Transcriptome and Metabolome Reveals Molecular Responses in Eriocheir sinensis with Hepatopancreatic Necrosis Disease

SIMPLE SUMMARY: There are still many doubts about the etiology and pathogenic mechanisms of Chinese mitten crab hepatopancreatic necrosis disease (HPND). In the present study, new insights into the molecular responses of diseased crabs were found by integrating transcriptomics and metabolomics. The results show that the immune system, metabolic capacity, antioxidant system, detoxification capacity, and nervous system of HPND-affected crabs were impacted, and these changes may be related to the pathological mechanism of HPND. Furthermore, we suspect that functional hypoxia may be involved in the progression of HPND, which provides new insights into the pathogenic mechanism of HPND. In conclusion, based on our findings, we further confirmed that HPND could be mainly caused by abiotic factors. ABSTRACT: Hepatopancreatic necrosis disease (HPND) is a highly lethal disease that first emerged in 2015 in Jiangsu Province, China. So far, most researchers believe that this disease is caused by abiotic factors. However, its true pathogenic mechanism remains unknown. In this study, the effects of HPND on the metabolism and other biological indicators of the Chinese mitten crab (Eriocheir sinensis) were evaluated by integrating transcriptomics and metabolomics. Our findings demonstrate that the innate immunity, antioxidant activity, detoxification ability, and nervous system of the diseased crabs were affected. Additionally, metabolic pathways such as lipid metabolism, nucleotide metabolism, and protein metabolism were dysregulated, and energy production was slightly increased. Moreover, the IL-17 signaling pathway was activated and high levels of autophagy and apoptosis occurred in diseased crabs, which may be related to hepatopancreas damage. The abnormal mitochondrial function and possible anaerobic metabolism observed in our study suggested that functional hypoxia may be involved in HPND progression. Furthermore, the activities of carboxylesterase and acetylcholinesterase were significantly inhibited, indicating that the diseased crabs were likely stressed by pesticides such as pyrethroids. Collectively, our findings provide new insights into the molecular mechanisms altered in diseased crabs, as well as the etiology and pathogenic mechanisms of HPND.