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A study was conducted, in association with the Alabama and Mississippi National Estuarine Research Reserves (NERRs) in the Gulf of Mexico (GoM) as well as the Georgia, South Carolina, and North Carolina NERRs in the Southeast (SE), to evaluate the impacts of coastal development on tidal creek sentinel habitats, including potential impacts to human health and well-being. Uplands associated with Southeast and Gulf of Mexico tidal creeks, and the salt marshes they drain, are popular locations for building homes, resorts, and recreational facilities because of the high quality of life and mild climate associated with these environments. Tidal creeks form part of the estuarine ecosystem characterized by high biological productivity, great ecological value, complex environmental gradients, and numerous interconnected processes. This research combined a watershed-level study integrating ecological, public health and human dimension attributes with watershed-level land cover data. The approach used for this research was based upon a comparative watershed and ecosystem approach that sampled tidal creek networks draining developed watersheds (e.g., suburban, urban, and industrial) as well as undeveloped sites (Holland et al. 2004, Sanger et al. 2008). The primary objective of this work was to define the relationships between coastal development with its concomitant land cover changes, and non-point source pollution loading and the ecological and human health and wellbeing status of tidal creek ecosystems. Nineteen tidal creek systems, located along the Southeastern United States coast from southern North Carolina to southern Georgia, and five Gulf of Mexico systems from Alabama and Mississippi were sampled during summer (June-August) 2005, 2006 (SE) and 2008 (GoM). Within each system, creeks were divided into two primary segments based upon tidal zoning: intertidal (i.e., shallow, narrow headwater sections) and subtidal (i.e., deeper and wider sections), and watersheds were delineated for each segment. In total, we report findings on 29 intertidal and 24 subtidal creeks. Indicators sampled throughout each creek included water quality (e.g., dissolved oxygen, salinity, nutrients, chlorophyll-a levels), sediment quality (e.g., characteristics, contaminant levels including emerging contaminants), pathogen and viral indicators (e.g., fecal coliform, enterococci, F+ coliphages, F- coliphages), and abundance and tissue contamination of biological resources (e.g., macrobenthic and nektonic communities, shellfish tissue contaminants). Tidal creeks have been identified as a sentinel habitat to assess the impacts of coastal development on estuarine areas in the southeastern US. A conceptual model for tidal creeks in the southeastern US identifies that human alterations (stressors) of upland in a watershed such as increased impervious cover will lead to changes in the physical and chemical environment such as microbial and nutrient pollution (exposures), of a receiving water body which then lead to changes in the living resources (responses). The overall objective of this study is to evaluate the applicability of the current tidal creek classification framework and conceptual model linking tidal creek ecological condition to potential impacts of development and urban growth on ecosystem value and function in the Gulf of Mexico US in collaboration with Gulf of Mexico NERR sites. The conceptual model was validated for the Gulf of Mexico US tidal creeks. The tidal creek classification system developed for the southeastern US could be applied to the Gulf of Mexico tidal creeks; however, some differences were found that warrant further examination. In particular, pollutants appeared to translate further downstream in the Gulf of Mexico US compared to the southeastern US. These differences are likely the result of the morphological and oceanographic differences between the two regions. Tidal creeks appear to serve as sentinel habitats to provide an early warning of the ensuing harm to the larger ecosystem in both the Southeastern and Gulf of Mexico US tidal creeks.