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Reyes-López, Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona 08193 Bellaterra, Spain, E-mail: Lluis. [email protected]: Allostatic load, Fish, Inflammatory network, Regulatory systems Fish and the other vertebrates subjected to challenges and stressors display a number of responses that involve many physiological compartments and mechanisms.In this review, this role is revisited, in particular focusing in the head kidney, a unique structure with many physiological functions in fish.The repertoire of immune cells and molecules involved in the immune response is shown, paying particular attention to those that present an evolutive and functional difference compared to what is known in mammals.Lesions or parasite occurrence in skin or gills, or local environmental changes in the gut caused by diet composition or pathogens, may also initiate local changes triggering the cytokines- or neural peptides-mediated immune response .The physiological effects of waterborne fish diseases remain species-specific, but a common pattern emerges: in fish, the activation of Hypothalamic-Pituitary-Interrenal (HPI) and Brain-Sympathetic-Chromaffin cell (BSC) axis directs the neuroimmunoendocrine crosstalk , and the head kidney harbours the cellular scaffold that integrates the stress response.