Atlantic Salmon aquaculture in the UK is facing an existential threat in the form of poor gill health. Losses are mounting every year, threatening the viability of an industry that is worth >£1Billion to the UK economy and represented the largest UK food export during 2021 but has decreased due to ongoing health challenges. Gills are vital organs, with functions in gas exchange, water balance and excretion of nitrogenous waste. Salmon gills are in constant and direct contact with the constantly changing marine environment, the 'Achilles heel' of this economically important fish. Organisms in the plankton such as harmful algae and micro-jellyfish are the principal cause of gill damage and inflammation, but little is known about which plankton species are detrimental to fish health. Warming surface waters are causing these planktonic agents to bloom more frequently and in greater numbers. Other parasitic organisms, for example amoeba causing amoebic gill disease, exacerbate gill damage. At present, aquaculture producers have few tools at their disposal to predict, avoid or treat the gill damage that occurs. New approaches are required to fully understand the biology of this system and to enable salmon producers to mitigate losses. For example, to understand which planktonic organisms are causing gill damage a systematic approach is required to reveal the hidden diversity of plankton communities. The University of Glasgow has recently shown 'proof of concept' at two aquaculture sites that daily environmental DNA metabarcoding direct from salmon pens, alongside rigorous statistical analysis, can reveal plankton diversity and provide 'early warning' for damaging bloom events. Meanwhile, the University of Aberdeen has developed a panel of gene expression biomarkers that has the potential to detect early gill damage before it becomes irreversible. Selective breeding of more resilient salmon is the ultimate tool to mitigate against salmon losses due to planktonic challenge. Working with Benchmark Genetics, the Roslin Institute has shown that salmon can be bred have resistance to amoebic gill disease. Progress can also be made towards breeding salmon more resilient to gill challenge from harmful plankton if the complexity of these planktonic communities can be simulated under laboratory conditions. The current project is an Industrial Partnership Award which includes contributions and involvement from Scotland's three largest salmon producers (MOWI, Scottish Sea Farms, Bakkafrost), Benchmark Genetics (a salmon selective breeding company) and EsoxBio (a molecular diagnostics start-up). Academic partners are the Universities of Glasgow, Aberdeen, Stirling, and Edinburgh. In a first objective, the project will undertake systematic sampling of planktonic communities and salmon gill biomarkers over three years at nine sites to rigorously identify which planktonic species and which gill biomarkers predict gill damage. Secondly, via in-house marine aquaria and in vitro cellular models, the role that cleaning biofouling from net pens has in releasing harmful organisms into the plankton will be explored in the context of acute gill inflammation. Thirdly, using innovative mobile experimental aquaria at three shore-side aquaculture sites, complex planktonic challenges will be simulated to enable a replicated genome wide association study (GWAS) for salmon resilience to gill damage as well as to trial multiple interventions to mitigate gill damage. The GWAS represents a first step towards a selective breeding program; the intervention study will inform aquaculture producers on immediate steps that can be taken to combat losses. In a final objective, data streams from across the project will flow into an integrated mathematical model that will reveal the environmental and molecular mechanisms that underpin salmon responses to harmful plankton as well as predict the likely success of gill health interventions in the future.