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As an ectothermic species, the American lobster (\n                  <jats:italic>Homarus americanus<\/jats:italic>\n                  ) relies on physiological and neurochemical mechanisms to maintain homeostasis under varying environmental conditions. To elucidate the role of neuropeptides in neuronal plasticity and systemic adaptation to temperature fluctuations, we employed a quantitative mass spectrometry-based approach to probe key neuropeptides involving thermal adaptation in four lobster neural tissues at three temperatures: 4 \u00b0C (cold), 11 \u00b0C (control), and 18 \u00b0C (warm). Peptidomic profiling revealed a global reduction in peptide abundance during cold exposure, alongside coordinated, tissue-specific reconfigurations of the neuropeptidome between experimental groups. Cold exposure led to a significant downregulation of RFamide, leucokinin, and pyrokinin peptides in the commissural ganglia, whereas B-type allatostatin (AST-B), natalisin, and RYamide peptides were drastically elevated in the brain of warm-acclimated animals, with comparatively fewer detectable peptide abundance changes in the sinus gland and the stomatogastric ganglion. Collectively, our findings elucidate neuropeptide signaling pathways underlying thermal tolerance and adaptive resilience in\n                  <jats:italic>Homarus americanus<\/jats:italic>\n                  , offering insights into the survival mechanism and neurochemical basis of neural circuits in response to thermal acclimation.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" fig-type=\"figure\" orientation=\"portrait\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"710231v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                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