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This work is the first, the purpose of which was a comprehensive assessment of the ecological state of the lower reaches of the Zarafshan River using bioindication of water quality by diatoms based on species’ ecological preferences, pollution indices, statistics, and ecological mapping. A total of 198 species and subspecies of diatoms were first identified from 195 samples collected four times a year at six sites in the lower reaches of the Zarafshan River in 2009–2015. The richest species were Cymbella, Navicula, and Nitzschia. Pleurosira laevis, resistant to salinity, was first found in aquatic habitats in Uzbekistan. Bioindicators of nine environmental variables make up 91% of the list. Distribution analysis of variables, pollution indices (SLA—SládečDek index of saprobity), and toxicity indices (WESI—Water Ecosystem State Index) show increases in salinity, turbidity, and decreases in organic pollution downstream. The source of acidification can be the Navoi region. We found an increase in the ability to self-purify with an increase in species richness and abundance of diatoms in the lower part of Zarafshan. Thus, the ecosystem of the studied part of the river successfully copes with the incoming pollution from the middle part of Zarafshan and demonstrates some stability and successful self-purification with a water quality class of 2–3. The first studied lower reaches of the ecosystem of the Zarafshan River using bioindicators, statistics, and ecological mapping show that the problem of aridization in Central Asia does not necessarily lead to degradation of the river ecosystem and an increase in pollution, but with rational water use can improve water quality and self-purification processes. Hence, diatoms can be good indicators of river water quality in a semi-arid region and reflect the climate and anthropogenic load change. We recommend that attention be paid to nutrient and turbidity management and to expand state monitoring points to the lower part of the river up to the Karakul region.

Diatom Algae-Indicators of Water Quality in the Lower Zarafshan River, Uzbekistan