MELBOURNE, Fla. — The first hint that something was amiss here, in the shallow lagoons and brackish streams that buffer inland Florida from the Atlantic’s salt water, came last summer in the Banana River, just south of Kennedy Space Center. Three manatees — the languid, plant-munching, over-upholstered mammals known as sea cows — died suddenly and inexplicably, one after another, in a spot where deaths were rare.

A year later, the inquiry into those deaths has become a cross-species murder mystery, a trail of hundreds of deaths across one-third of the Indian River estuary, one of the richest marine ecosystems in the continental United States.

Along 50 miles of northern estuary waters off Brevard County and the Kennedy space complex, about 280 manatees have died in the last 12 months, 109 of them in the same sudden manner as the Banana River victims. As the manatee deaths peaked this spring, hundreds of pelicans began dying along the same stretch of water, followed this summer by scores of bottlenose dolphins.

The cause continues to evade easy explanation. But a central question is whether the deaths are symptoms of something more ominous: the collapse of the natural balance that sustains the 156-mile estuary’s northern reaches.