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Using transverse cross-sectional transects, a survey of 31 km of the non-tidal Potomac River was conducted from White’s Ferry, Virginia to Brunswick, Maryland, USA, between June and September in 2013 through 2015 to assess a recurring benthic cyanobacteria bloom. Abundant benthic cyanobacteria blooms were detected during the 2014 and 2015 sampling seasons and the primary taxon was identified morphologically and molecularly as Planktothrix cf. isothrix. When present, P. cf. isothrix blooms were concentrated from river center to the Maryland shoreline. This pattern was correlated with significantly greater benthic chlorophyll-a and phycocyanin concentrations. In an apparent response to the P. cf. isothrix blooms in the study site, aquatic macroinvertebrate community assemblages were significantly different between areas with extensive benthic cyanobacterial growth compared to areas without cyanobacterial growth. Within the P. cf. isothrix mats, the percentage of pollution sensitive taxa was lower and the percentage of pollution tolerant taxa was greater. These data suggest that P. cf. isothrix can act as an ecosystem disruptor through direct impacts to the aquatic macroinvertebrate abundance and community structure within this section of the freshwater, non-tidal Potomac River.