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However, these effects are highly variable and depend on species identity, strain-specific traits, and local environmental conditions. Key drivers include rising sea surface temperatures, changes in salinity resulting from altered precipitation patterns and runoff, and elevated CO2 levels leading to ocean acidification. Heterosigma akashiwo, a euryhaline raphidophyte responsible for the widespread killing of fish, is particularly responsive to these changes. This study investigated the combined effects of temperature, salinity, and CO2 concentration on the growth, yield, and cell membrane permeability of H. akashiwo using a Design of Experiment (DOE) approach. DOE facilitates a detailed and systematic analysis of multifactorial interactions, enabling a deeper understanding of complex relationships while maximizing efficiency and minimizing the use of experimental resources. The results revealed that growth and yield were maximized at higher temperatures and salinities, whereas cell permeability increased under cooler, less saline, and lower CO2 conditions. These findings suggest that projected future ocean conditions may enhance biomass production while potentially reducing cellular permeability and, by extension, toxicity. This study highlights the value of the DOE framework in identifying key interactions among environmental drivers of HABs, offering a practical foundation for future predictive modeling under climate change scenarios.<\/jats:p>","DOI":"10.3390\/toxins17050259","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T06:31:27Z","timestamp":1747809087000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Growth Response and Cell Permeability of the Fish-Killing Phytoflagellate Heterosigma akashiwo Under Projected Climate Conditions"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6351-9393","authenticated-orcid":false,"given":"Malihe","family":"Mehdizadeh Allaf","sequence":"first","affiliation":[{"name":"Department of Chemical and Biochemical Engineering, Western University, London, ON N6A 5B9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles G.","family":"Trick","sequence":"additional","affiliation":[{"name":"Department of Physical and Environmental Sciences, University of Toronto, Toronto, ON M1C 1A4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.2216\/i0031-8884-32-2-79.1","article-title":"Review of harmful algal blooms and their apparent global increase","volume":"32","author":"Hallegraeff","year":"1993","journal-title":"Phycologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1007\/BF02804901","article-title":"Harmful algal blooms and eutrophication: Nutrient sources, compositions, and consequences","volume":"25","author":"Anderson","year":"2002","journal-title":"Estuaries"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"198","DOI":"10.5670\/oceanog.2005.54","article-title":"The role of eutrophication in the global proliferation of harmful algal blooms: New perspectives and new approaches","volume":"18","author":"Glibert","year":"2005","journal-title":"Oceanography"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/j.1529-8817.2010.00815.x","article-title":"Ocean climate change, phytoplankton community responses, and harmful algal blooms: A formidable predictive challenge","volume":"46","author":"Hallegraeff","year":"2010","journal-title":"J. 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